Evaluating the real-world vaccine effectiveness using a regression discontinuity design / 中华流行病学杂志

Estimating the actual real-world effectiveness of the vaccine is an essential part of the post-marketing evaluation. This regression discontinuity design (RDD) using observational data is designed to quantify the effect of an intervention when eligibility for the intervention is based on a defined cutoff as age, making it suited to estimate vaccine effects. This approach can avoid the high cost and ethical issues; overcome difficulties in the organization and practice process in randomized controlled trials, which leads to a higher level of causal inference evidence and more realistic results. Here, we describe key features of RDD in general, and then specific scenarios, with examples, to illustrate that RDD are an essential tool for advancing our understanding of vaccine effects.

Advances in research of interchangeable immunization with live attenuated Japanese encephalitis vaccines and inactivated vaccines / 中华预防医学杂志

Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia and the Western Pacific, which mainly invades central nervous system. Vaccination is the most important strategy to prevent JE. Currently, both live attenuated Japanese encephalitis vaccines (JE-L) and inactivated vaccines (JE-I) are in use. Due to the supply of vaccines and the personal choice of recipients, there will be a demand for interchangeable immunization of these two vaccines. However, relevant research is limited. By reviewing domestic and foreign research evidence, this article summarizes the current situation of the interchangeable use of JE-L and JE-I, and makes recommendations when the interchangeable immunization is in urgent need, so as to provide reference for practical vaccination and policymaking in China.

The dual mTORC1/2 inhibitor AZD2014 inhibits acute graft rejection in a rat liver transplantation model / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of AZD2014, a dual mTORC1/2 inhibitor, against acute graft rejection in a rat model of allogeneic liver transplantation.@*METHODS@#Liver transplantation from Lewis rat to recipient BN rat (a donor-recipient combination that was prone to induce acute graft rejection) was performed using Kamada's two-cuff technique. The recipient BN rats were randomized into 2 groups for treatment with daily intraperitoneal injection of AZD2014 (5 mg/kg, n=4) or vehicle (2.5 mL/kg, n=4) for 14 consecutive days, starting from the first day after the transplantation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels of the rats were measured 3 days before and at 1, 3, 5, 7, 10, and 14 days after the transplantation, and the survival time of the rats within 14 days were recorded. Immunohistochemical staining was used to examine the expressions of CD3 and Foxp3 in the liver graft, and acute graft rejection was assessed using HE staining based on the Banff schema.@*RESULTS@#Three rats in the control group died within 14 days after the surgery, while no death occurred in the AZD2014 group, demonstrating a significantly longer survival time of the rats in AZD2014 group (χ2=4.213, P=0.04). Serum ALT, AST and TBIL levels in the control group increased progressively after the surgery and were all significantly higher than those in AZD2014 group at the same time point (P < 0.05). Pathological examination revealed significantly worse liver graft rejection in the control group than in AZD2014 group based on assessment of the rejection index (P < 0.01); the rats in the control group showed more serious T lymphocyte infiltration and significantly fewer Treg cells in the liver graft than those in AZD2014 group (P < 0.01).@*CONCLUSIONS@#AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.

Characteristics of school public health emergencies in Zhejiang Province / 预防医学

Objective To analyze the characteristics of school public health emergencies in Zhejiang Province, and to provide current suggestions for prevention and control. Methods A descriptive epidemiological analysis was conducted for the public health emergencies occurred in schools from 2014 to 2016 in Zhejiang Province. The data was derived from Emergency Public Reporting System. Results A total of 100 public health emergencies occurred in schools and 3 784 cases were reported during 2014-2016 in Zhejiang Province, meanwhile no death occurred. There were two peak seasons every year for the emergency report. Forty percent of the emergencies were reported during November to January of the following year, and 31.00 % were during April to May. The emergencies occurred on all the municipal districts when Ningbo accounted for 50.00%. The schools and kindergartens in rural area, town and urban area reported 37, 28 and 35 emergencies respectively. The main etiology of emergencies included varicella(37.00%), hand-foot-mouth disease(29.00%), norovirus(22.00%). The median duration of varicella outbreaks was 31.67d, which was longer than others. The scale of influenza and norovirus outbreaks were larger, and the median cases were 76 and 49 respectively. The time of emergencies detecting was significantly different between different detecting patterns. Conclusion The prevention and control of school emergencies was still urgently. There were still some deficiencies in the identification and active reporting of the epidemic, which need to be solved, while taking advantage of the surveillance system for sick absence. The future strategies should focused on reinforcing immunization and improving health habits to promote school health.

LKB1 regulates epithelial-mesenchymal transition in Peutz-Jeghers hamartoma and intestinal epithelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the molecular mechanism by which LKB1 regulates epithelial-mesenchymal transition (EMT) in Peutz-Jeghers hamartoma and intestinal epithelial cells.</p><p><b>METHODS</b>Immunohistochemistry was used to detect gene expression of LKB1, E-cadherin, and vimentin in 20 hamartoma tissues and 10 normal intestinal tissues, and collagen fiber deposition was analyzed using Masson trichrome staining. Normal intestinal epithelial NCM460 cells were transfected with LKB1 shRNA plasmid or negative control via lentiviral vectors, and the role of LKB1 in cell polarization and migration were determined using CCK8 and Transwell assays. Western blotting, quantitative real-time PCR (qPCR) and immunofluorescence were used to assess the alterations of EMT markers in the cells with LKB1 knockdown.</p><p><b>RESULTS</b>Compared with normal intestinal tissues, hamartoma polyps showed significantly decreased LKB1 and E-cadherin expressions and increased vimentin expression with increased collagen fiber deposition. The cells with LKB1 knockdown exhibited enhanced cell proliferation and migration activities (P<0.01). Western blot analysis, qPCR and immunofluorescence all detected decreased E-cadherin and increased N-cadherin, vimentin, Snail, and Slug expressions in the cells with LKB1 knockdown.</p><p><b>CONCLUSION</b>s LKB1 deficiency triggers EMT in intestinal epithelial cells and Peutz-Jeghers hamartoma, suggesting that EMT can serve as the therapeutic target for treatment of Peutz-Jeghers syndrome.</p>

Establishment of A Myelodysplastic Syndrome Transformed to Leukemia Cell Line Stably Expressing Green Fluorescent Protein / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To establish a myelodysplastic syndrome transformed to leukemia cell line stably expressing green fluorescent protein (GFP), and to evaluate its biological characteristics and applications.</p><p><b>METHODS</b>SKM-1 cells were transfected by lentiviral particles with vector of GFP. The GFP positive single cell clone was isolated by limiting dilution and continued being cultured. The cells were injected into mice subcutaneously and were screened in vivo. Then SKM-1/GFP cells were obtained after tumour plaque was separated and cultivated. The cell morphology was observed by fluorescence microscopy. The GFP expression was further detected by flow cytometry. The cell proliferation was analysed by CCK-8 assay. SKM-1/GFP cells were inoculated to subcutaneous tissue of the immunodeficiency mice. The growth and invasion of the tumour were observed after tumour formation.</p><p><b>RESULTS</b>No differences in cell morphology and growth characteristics were observed between SKM-1 cells and SKM-1/GFP cells. The rate of GFP expression was 100%. No differences in cell proliferation were observed between SKM-1 cells and SKM-1/GFP cells. The tumour mass was observed after 14 days of subcutaneous vaccination in NOD/SCID mice. Spontaneous fluorescence from plaque was observed by living fluorescence microscopy at 30th day after vaccination. Homogenous GFP positive cells were observed by fluorescence microscopy in the frozen section of tumour mass. The invasion of SKM-1/GFP cells was also detected in heart, liver, stomach and kidney of mice.</p><p><b>CONCLUSION</b>A myelody-splastic syndrome transformed to leukemia cell line stably expressing green fluorescent protein has been established successfully, which can track tumor cell sensitively and can be applied to the research of minimal residual leukemia. The establishment of SKM-1/GFP cells may serve as a powerful means for studing myelodysplastic syndrome transformation.</p>

A study on the prevalence of chronic diseases and risk factors control among the elderly of community health management in Zhejiang Province / 预防医学

Objective To learn the prevalence of chronic diseases and risk factors control among the elderly of community health management in Zhejiang Province.Methods The elderly residents over 60 years of urban areas in Zhejiang Province were investigated through multi-stage stratified sampling,and key health examination information in year 2015 of respondents was collected.The prevalence of chronic diseases and risk factors control were analyzed among the respondents who had accepted community elderly health management.Results Among 1 215 elderly who accepted community health management,self-reported prevalence rate of common chronic diseases was 84.36％,with hypertension 60.66％,cataract 21.32％ and diabetes 20.58％.The control rates of hypertension and diabetes were 64.04％ and 60.00％,respectively.The proportions of light weight,normal weight,overweight and obesity were 3.51％,50.04％,35.51％ and 10.94％ respectively.The prevalence rate of central obesity was 54.75％,female (59.00％) higher than male (48.47％) (P ＜ 0.001).The proportions of normal,borderline high and abnormal total cholesterol (TC) were 66.75 ％,23.95％ and 9.30％ respectively.The proportions of normal,borderline high and abnormal triglyceride (TG) were 65.73％,17.05％ and 17.22％ respectively.The proportions of normal TC and TG were both lower in female (both 61.94％) than those in male (TC:74.07％、TG:71.52％) (P ＜ 0.05).The prevalence rates of hypertension (OR =1.41,95％ CI:1.11-1.79),cataract (OR =2.19,95％ CI:1.65-2.91),coronary heart disease (OR =1.59,95％ CI:1.14-2.21)and cerehmvascular disease (OR =2.06,95 ％ CI:1.29-3.30)were significantly increased in the 75 years group than that in the 60-74 years group.The prevalence of cerehrovascular disease in elderly men in the age group of 60 -74 (OR =1.73,95％ CI:1.09-2.75) and chronic obstructive pulmonary disease (OR =2.41,95％ CI:1.04-5.59) were higher than that in female,while the prevalence of rheumatoid arthritis (OR =0.54,95％CI:0.35-0.84)were lower than that in male.Conclusion Among the elderly who accepted community health management,the prevalence rate of chronic diseases is similar with the general elderly population in Zhejiang Province.Female central obesity and blood lipids control should be strengthened in the community.

Claudin-3 expression in colorectal carcinoma and its significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of claudin-3 in colorectal carcinoma and its association with the occurrence, progression and prognosis of colorectal cancer.</p><p><b>METHODS</b>Forty surgical specimens of colorectal carcinoma and 22 adjacent normal tissues resected between October, 2010 and January, 2013 at Nanfang Hospital were examined for claudin-3 expression using immunohistochemistry, which was analyzed in association with the clinicopathological parameters and the survival of the patients.</p><p><b>RESULTS</b>Claudin-3 was expressed mainly on the cell membrane, and its positivity rate was significantly higher in cancer tissues than in normal tissues (92.50% vs 59.09%, P<0.05). In 13 cases claudin-3 expression was detected in both the cancer tissues and adjacent normal tissues with average expression scores of 4.538 and 3.269, respectively (P<0.05). In the cancer tissues, the strongly positive expression rate was significantly higher in poorly differentiated tissues (85.71%) than in well (21.43%) and moderately (36.48%) differentiated tissues (P<0.05), and was higher in cases with lymph node metastasis than in those without (61.11% vs 22.72%, P<0.05). The strongly positive expression rate of claudin-3 was not correlated with the patients'age, gender, tumor location or tumor size (P>0.05). Of the 33 cancer patients followed up, 14 had a postoperative survival time no longer than 3 years and 19 had longer survival time, and their average expression scores differed significantly (4.50 vs 3.526, P<0.05).</p><p><b>CONCLUSION</b>Claudin-3 is over-expressed in colorectal cancer tissues, and its high expression may promote the occurrence and progression of colorectal cancer. Claudin-3 may serve as a molecular biomarker for early diagnosis and prognostic evaluation.</p>

Regional variations of basic public health services implementation in Zhejiang Province based on the Gini coefficient / 预防医学

Objective To explore regional variations of basic public health services implementation in Zhejiang Province at prefectural,county and township level,respectively.To find key problems which obstacle the equalization of basic public health services in Zhejiang Province.Methods Descriptive analysis was made on surveillance data of basic public health services in Zhejiang Province,2014.Gini coefficient of key indicators was calculated at prefectural,county and township level,respectively.To the key indicator with higher Gini coefficient,Lorenz curve was plotted and Gini coefficient of each prefectural-level city was calculated.Results An increasing tendency from prefectural to township level was showed in Gini coefficient of all twenty-five analyzed indicators.The Gini coefficient at township level was 0.497 for the average financial fund per migrant person,and the highest prefectural -level cities were Taizhou (0.709 ),Lishui (0.838 ), Quzhou(0.918).The Gini coefficient at township level of other indicators were 0.314 and 0.235 for the children and elderly health management of traditional Chinese medicine,and lower than 0.05 for maternal &children health care, immunization,and coverage rate of electronic health record,and between 0.066 to 0.179 for health management of chronic disease and severe mental illness patients.Conclusion Average financial fund per migrant person and health management of traditional Chinese medicine are current major problems which obstacle the equalization of basic public health services in Zhejiang Province.

An analysis on the correlations between the scarlet fever and meteorological factors with generalized additive model / 预防医学

Objective To explore the correlations between the scarlet fever and meteorological factors in Zhejiang Province. Methods The data which was been analyzed including month case of scarlet fever and meteorological factors from JAN 2005 to DEC 201 4,were analyzed for the degree and characteristic of the correlations between the scarlet fever and meteorological factors with generalized additive model(GAM).Results There were negative correlation between scarlet fever and meteorological factors including water vapor pressure and hours of sunshine.There were complex nonlinear correlations between scarlet fever and meteorological factors including precipitation,average barometric pressure,average wind speed and average temperature .The relationship between scarlet fever and meteorological factors including average barometric pressure,average wind speed and average temperature showed approximate quadratic function.The precipitation above 3 500(0.1 mm),average barometric pressure above 1 0 200(0.1 hPa)and under 1 0 050(0.1 hPa),average wind speed between 1 8.7 -23.6 (0.1 m/s)and average temperature between 1 00 -250 (0.1 ℃) were the suitable meteorological condition for scarlet fever.Conclusion There were complex nonlinear correlations between the scarlet fever and meteorological factors.Precipitation,average barometric pressure,average wind speed and average temperature may be associated with the incidence of scarlet fever.

A study on the estimation of type I and type II error of national basic public health services supervision through random sampling / 预防医学

Objective Estimate type I and type II error probability (α,β)of sampling deduction,using sample size set in national basic public health services supervision.Methods Assuming a series of population indicator value of supervised area,αand βwas calculated based on binomial & hypergeometric distribution theory according to the sample size and indicator requirements set in supervision plan.Results When the population indicator value of supervised area was just equal to indicator requirements,probability of type I error was as follows,health record utilization rate(0.41 ),health record qualification rate(0.26),children systematic management rate(0.32),postpartum visit rate(0.32),the elderly health examination form completion rate (0.35 ),standard administration rate of patients with hypertension or diabetes (0.37),control rate of blood pressure of hypertension patients(0.34),control rate of blood glucose of diabetes patients (0.43),standard administration rate of severe mental illness patients(0.50).When the population indicator value of supervised area was 0.05 lower than indicator requirements,probability of type II error of those indicator was as follows, 0.41,0.54,0.53,0.53,0.51,0.50,0.57,0.47,0.38.Conclusion Current sample sizes of all indicators result in weak sensitivity of unqualified area detection.In order to avoid mistake,the sample size should be improved.

Research Progress on Gene Expression Abnormality of Hematopoietic Stem/Progenitor Cells in Myelodysplastic Syndromes / 中国实验血液学杂志

Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disease involving one or more series of hematopoietic cells. Its pathogenesis is still unclear. No effective targeted drug is available to prevent this disease progression. MDS originates in hematopoietic stem cells. Recent researches found that the complex abnormal gene expression occurred in bone marrow CD34⁺ cells plays a key role in development of MDS. Some of these genes are closely related with the patient's prognosis and survival, such as DLK1, ribosomal transcripts gene, Toll-like receptors gene, EPA-1 and interferon-stimulated genes. Due to heterogeneity of this disease, abnormal gene expression profiles in bone marrow CD34⁺ cells are closely associated with particular FAB or cytogenetic subtypes. To elucidate the pathogenesis of MDS and investigate its therapeutic target, this article reviews progress of researches on abnormal gene expression profiles of hematopoietic stem/progenitor cells in low-risk, high-risk patients and MDS patients who carry common cytogenetic abnormalities.

Establishment of Primary Adult MDS Nested Case-Control Study Cohort and Study of Risk Factors Associated with MDS Evolution to Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To establish a nested case-control study cohort in myelodysplastic syndrome (MDS) patients and investigate the clinical characteristics, WHO subtype and risk factors associated with MDS evolution to leukemia of this cohort.</p><p><b>METHODS</b>All patients, ≥18 years of age, provided by 24 Shanghai hospitals with initial clinical findings consistent with a hematopoietic abnormality between June 2003 and April 2007, were the candidates for inclusion in this study. The blood and bone marrow samples of every patient should be provided at baseline. Diagnosis was made by incorporating morphologic, immunophenotypic, cytogenetic and molecular features according to WHO classification criteria. Cytogenetic analysis was performed using conventional G-banding karyotyping and fluorescence in situ hybridization (FISH) techniques. Cumulative risk of evolution was estimated by Kaplan-Meier method. Prognostic factors were evaluated by univariate Log-rank method and multivariate Cox proportional hazard models.</p><p><b>RESULTS</b>A total of 435 patients were diagnosed as MDS. The median age of MDS onset was 58(18-90) years, with 248 male patients and 187 female patients (male: female 1.33: 1). The percentage of cases with refractory cytopenia with multilineage dysplasia (RCMD) was the highest (65.5%), while that of refraetory anemia (RA) (2.3%), refractory anenia with ring sideroblast (RARS) (1.1%) and 5q-syndrome (0.5%) was lower. Trisomy 8 (+8) was the most common chromosome abnormalities (71 cases, 12.7%). The mean follow-up time was 20.3 (4.2-57.1) months. Cases were patients with evolution by the end of follow-up, while controls were patients without evolution by that time. Case group included 41 patients and control group included 342 patients. Univariate analysis showed that the age, sex, WHO subtype, WBC count, absolute neutrophil count (ANC), IPSS cytogenetic subgroup, IPSS group and bone marrow blast percentage were significant risk factors for leukemia-free survival (LFS). Multivariate analysis of COX model showed that the age, sex, WHO subtype, IPSS cytogenetic subgroup and bone marrow blast were independent risk factors for LFS.</p><p><b>CONCLUSION</b>A nested case-control study cohort of MDS patients is established. The clinical characteristics and WHO subtype of MDS patients in Chinese Shanghai are different from that in Western countries. The independent risk factors for MDS evolution are age, sex, WHO subtype, IPSS cytogenetic subgroup and bone marrow blast percentage.</p>

Research progress on genes associated with transformation of myelodysplastic syndromes to acute myeloid leukemia / 中国实验血液学杂志

Myelodysplastic syndrome (MDS) is highly heterogeneous clonal hematological malignancy, having a high rate of progression to acute myeloid leukemia (AML). With the rapid development of molecular biological techniques, plenty of gene mutations were found to have close relationships with the transformation from MDS to AML. SRSF2 is a RNA splicing-related gene, which mutation may prompt a poor prognosis, and have a higher rate of progressing to AML. DNMT3A plays an important role in DNA methylation, its mutation often indicate a worse overall survival and a more rapid progression to AML. ASXL1 regulates the synthesis of histone, which frameshift mutations are molecular marks of an adverse outcome. IDH contains IDH1 and IDH2, which are related with the Krebs cycle. Patients with IDH1 mutation have a shorter overall survival and a higher risk of AML transformation than that of patients with wild-type IDH1, while IDH2 was a poor prognostic factor for overall survival in patients with lower-risk MDS. Another gene related with DNA methylation is TET2, which is the most frequently mutated gene in MDS known so far and it may act as tumor-suppressor gene, but the opinions on its impact on patients' outcomes are still controversial. Some studies show that its mutations relate to a shorter time to progression to AML. Because of the differentiations in patients' races, regions and clinical characteristics, the results of different studies are varied. In this review, the recent advances on these related genes are summarized.

Prognostic value of clinical characteristics and immunophenotypic biomarkers in 115 patients with primary central nervous system lymphoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Clinical outcome in patients with primary central nervous lymphoma (PCNSL) is variable and poorly predictable. This study investigated the association of clinical features and immune markers with prognosis of patients with PCNSL.</p><p><b>METHODS</b>One hundred and fifteen newly diagnosed PCNSL patients at the study institution were considered eligible for this study. Clinical characteristics and biochemical assay data were collected. Immunohistochemical staining of Cyclin D3, Cyclin E, Foxp1, and LMO2 were performed. All cases were followed-up regularly.</p><p><b>RESULTS</b>The common sites of involvement were frontal lobe (54.8%) and thalamus (16.5%). Diffuse large B-cell lymphoma composed of 96.5% of the cases. The median overall survival was 22 (4 - 41) months, and the 5-year survival rate was 22.8%. Age > 65 years, serum globulin > 40 g/L, large size of tumor, lymphocyte count ≥ 1 × 10(9)/L, and expression of Cyclin D3 and Cyclin E were associated with poor prognosis of PCNSL. Expressions of Foxp1, LMO2, and CD44 were not related to the survival. Expression of Cyclin E, large tumor size, and high serum globulin were independent prognostic factors for PCNSL.</p><p><b>CONCLUSIONS</b>PCNSL prognosis is relatively poor. Age, high tumor burden, higher lymphocyte count, expression of Cyclin D3, and Cyclin E are inferior prognostic factors for PCNSL.</p>

Up-and-down sequential method in determining median effective effect-site concentration (EC5O) of remifentanil required for inhibiting intubation-inducedhemodynamic responses in patients with parkinson's disease during target-controlled infusion of propofol / 第二军医大学学报

Objective To determine the median effective effect-site concentration (EC50) of remifentanil required to inhibit hemodynamic responses induced by intubation during target-controlled infusion (TCI) of propofol in patients with Parkinson' disease. Methods A1 (1 matched case control design was used in the study. Thirty-one ASA I E patients with Parkinson's disease undergoing general anesthesia were enrolled, and 31 controls were the hospitalized patients with non-Parkinson' disease during the same period (same sex, age ±3 years old). A TCI of propofol was used to maintain a predetermined effect-site concentrationof 3 fg/mL. The target effect-site concentration of remifentanil was determined by a modified Dixon' up-and-down sequential method. The initial target effect-site concentrations of remifentanil were 3 ng/mL in the two groups and the increments or decrements between the two consecutive patients were 0. 2ng/mL. A positive response meant that either the heart rate or the systolic blood pressure was elevated by 15% in the first5 min after intubation. Results There was no patient showed sign of muscle rigidity, and no patient recalled awareness during anesthesia in postoperative follow-up. During TCI of propofol, the EC50 of remifentanil required for inhibiting intubation induced hemodynamic responses for patientswith Parkinson' disease was 2. 20 ng/mL (95% confidence interval: 1. 86-2. 60 ng/mL). And the EC50f remifentanil required for control group was significantly higher than for patients with Parkinson' disease (2. 93 ng/mL, 95% confidence interval: 2. 72-3. 15 ng/mL). Conclusion When combined with TCI of propofol (target effect-site concentration 3 μg/mL), the EC50f remifentanil required for inhibiting intubation induced hemodynamic responses for patients with Parkinson' disease is less than that for non-Parkinson' disease.

Establishment of human homoharringtonine-resistant SKM-1 cell line and its biological characteristics / 中华血液学杂志

<p><b>OBJECTIVE</b>To establish a homoharringtonine (HHT)-resistant SKM-1 cell line and explore its biologic characteristics and mechanisms for drug resistance.</p><p><b>METHODS</b>The HHT-resistant SKM-1 cell line was established by repeatedly exposing the cells to comparatively large doses of HHT with a short-time duration, and gradually elevating the drug concentration to an endurable level. The morphology of the resistant and parental cell lines was observed through optical microscope. The MTT assay was used to determine the doubling time and the resistance index to draw growth curve. The immunophenotype, cell cycle distribution and DNR accumulation between SKM-1 and SKM-1/HHT were analyzed by flow cytometry, and the karyotypes by R-banding. Semi-quantitative real-time PCR was performed to evaluate the expression levels of mdr1, MRP and topo-IIa.</p><p><b>RESULTS</b>The HHT-resistant cell line SKM-1/HHT was eventually established following 7-month drug induction. Both the resistant and the parental cell lines were similar with regard to morphology and immunophenotype. The karyotypes of the former was more complicated with differences located in chromosome 20, X, 4, 5, 9 and 11. The resistant cell line had more G(1) phase cells (64.04% vs 41.91%), less S phase cells (34.92% vs 53.53%), and less G(2) phase cells (1.04% vs 4.56%) compared with the parental cell line. The SKM-1/HHT cell line showed significant drug resistance to HHT, VCR, DNR and etoposide, the resistance indices of HHT, VCR, DNR and etoposide were 17.94, 8.75, 5.99 and 13.76 respectively. DNR accumulation was impaired in SKM-1/HHT cell line as less fluorescence of DNR (698 ± 36 vs 858 ± 54). The expression of mdr1 increased dramatically in the resistant cell line, its 2(-ΔCt) value was 20.1 higher than that of the parental cell line \[(3.42 ± 0.46)×10(-2) vs (0.17 ± 0.01)×10(-2), P < 0.05\], while MRP also increased in the resistant by 3.56 folds \[(4.77 ± 0.87)×10(-3) vs (1.34 ± 0.56)×10(-3), P < 0.05\]; However there was a slightly decrease of topo-IIa, the ratio of the resistant to the parental calculated by their 2(-ΔCt) values was 0.619:1 \[(1.91 ± 0.30)×10(-4) vs (3.08 ± 0.21)×10(-4), P < 0.05\].</p><p><b>CONCLUSION</b>A HHT-resistant cell line SKM-1/HHT was established. The prominent overexpression of mdr1 may be the main cause for multidrug resistance.</p>

Expression of FOXP1 and cyclinE in primary central nervous system lymphoma and its significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the value of FOXP1 and Cyclin E gene in primary central nervous system lymphoma(PCNSL) of immunocompetent patients on prognostic significance.</p><p><b>METHODS</b>Clinical data of 71 patients with newly diagnosed PCNSL from 2002 to 2007 was analyzed retrospectively. Immunohistochemistry method (HRP-EnVision(TM)) was performed to observe the expression of FOXP1 and Cyclin E gene in tumor tissue samples. The survival was analyzed by Kaplan-Meier survival curve, survival factors analysis by the Log-rank test and COX proportional hazards regression model.</p><p><b>RESULTS</b>FOXP1 positive was observed in 35 of 51 patients (68.63%) and Cyclin E staining was present in 29 of 50 cases (58.00%). FOXP1(+) patients had a shorter overall survival (OS) than FOXP1(-) ones. 2-year OS rate in FOXP1(+) and FOXP1(-) patients were 23.33% and 73.56%, respectively(P = 0.0015). Cyclin E(+) patients had a shorter overall survival(OS) than cyclinE(-) ones. 2-year OS rate in Cyclin E(+) and Cyclin E(-) patients were 17.56% and 69.76%, respectively (P = 0.0017). Multivariate analysis showed that Cyclin E expression was an independent prognostic factor for shorter OS (P = 0.048). FOXP1 expression might be an important prognostic factor for shorter OS (P = 0.065).</p><p><b>CONCLUSION</b>Cyclin E expression is an independent prognostic factor and FOXP1 expression is a possible prognostic factor for poor clinical outcome in patients with PCNSL.</p>

Percutaneous transhepatic biliary radiofrequency and endoprothesis: a new therapy for malignant biliary obstruction / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore a new approach to the management of malignant biliary obstruction using percutaneous transhepatic biliary radiofrequency and endoprothesis.</p><p><b>METHODS</b>Percutaneous transhepatic biliary radiofrequency and endoprothesis were performed in 2 cases of malignant biliary obstruction, including 1 of hilar cholangiocarcinoma and 1 of pancreatic head carcinoma. The tumor was ablated with radiofrequency followed by placement of matched metal stents into the biliary duct.</p><p><b>RESULTS</b>The surgical procedures were carried out smoothly in the 2 cases. The symptoms of the patients were obviously improved after the operation with a significant decrease in the serum levels of total bilirubin, and CA-199 level decreased to the normal level in 1 case.</p><p><b>CONCLUSIONS</b>This new approach is safe for management of malignant biliary obstruction. Compared with the more conventional interventional therapy, radiofrequency can reduce the intraoperative bleeding and arrest the local tumor growth to promote the patency of the stent as well as the postoperative survival of the patients.</p>

Advances of study on prognostic factors of molecular biology in acute myeloid leukemia with normal cytogenetics / 中国实验血液学杂志

Acute myeloid leukemia (AML) is a group of diseases with a conspicuous heterogeneity. Following the development of cytogenetics, multiple reproducible chromosome aberrations have been discovered in AML, many of which not only are diagnostic markers for specific AML subtypes but also significant prognostic factors for determining complete remission (CR), relapse risk, and overall survival (OS). However, with the foundation of available chromosome analysis, a large group of acute myeloid leukemia (AML) patients, 40% to 49% of adults and 25% of children had not been found abnormality of chromosome karyotype under microscope. These so-called cytogenetically normal acute myeloid leukemia (CN-AML) patients have usually been classified in an intermediate-risk prognostic category. Nevertheless, the outcome of the CN-AML patients are varied in clinical studies, likely because there exist diverse gene mutations in these patients according to recent researches. Those mutations at the molecular level, on basis of which AML could be further classified, are significantly associated with CN-AML patients and offer potential targets for specific therapeutic studies. The review focuses on research advances abroad in this field including gene mutations suggesting bad prognosis such as FMS-related tyrosine kinase 3 gene mutation, Baalc gene and ETS-related gene hyperexpression, Wilms' tumor gene mutation and other gene mutations as well as gene mutations suggesting good prognosis such as nucleophosmin gene mutation, mixed lineage leukemia-partial tandem duplication, CCAAT/enhancer-binding protein α gene mutation.